Receptores nucleares formam uma superfamília de proteínas responsáveis pela regulação da expressão de genes. Estruturalmente, são formados por três domínios: um domínio N-terminal bastante variável, um domínio altamente conservado de ligação com o DNA e um domínio C-terminal, menos conservado, denominado domínio de ligação com o ligante (LDB). Diversos experimentos mostram que a interação com o ligante afeta a estrutura e a mobilidade da hélice C-terminal dos receptores nucleares (hélice 12 do domínio de ligação com o ligante), sendo o principal mecanismo de ativação e repressão da transcrição. As primeiras estruturas de LBDs de receptores nucleares revelaram importantes diferenças entre estruturas contendo ligantes (holo) e estruturas apo, principalmente no que diz respeito a posição da hélice 12: em estruturas apo, foi observada a H12 em uma conformação aberta, expondo o sítio de ligação com o ligante, enquanto que em estruturas holo, foi observada a H12 em uma conformação fechada, dobrada sobre o corpo do LBD e envolvendo completamente o ligante. Essa diferença sugeriu um mecanismo para a entrada e saída de ligantes do sítio de ligação denominado modelo da ratoeira, entretanto, esse modelo apresenta diversas inconsistências e tem sido desacreditado. Estudos experimentais e teóricos recentes mostram que a hélice 12 é mais móvel na ausência de ligantes, entretanto, esses estudos não fornecem evidencias de que o aumento da mobilidade da está associado com o deslocamento da H12 em relação ao corpo do LBD, como sugerido pelo modelo da ratoeira. Embora esteja claro que a hélice 12 é mais móvel na ausência de ligantes, a dimensão da variação conformacional sofrida pela hélice 12 ainda não está clara. Nesse trabalho buscamos a construção de um modelo capaz de dimensionar a mobilidade da hélice 12 através da comparação direta entre simulações de dinâmica molecular e experimentos de anisotropia de fluorescência resolvida no tempo. Utilizando simulações de dinâmica molecular reproduzimos experimentos de anisotropia de fluorescência acoplando a sonda cys-flúor a hélice 12 do PPARγ para estudar sua mobilidade. Mostramos que as observações experimentais só podem ser explicadas por conformações onde a sonda fluorescente permanece presa a superfície do LBD. Foi mostrado também que curvas de anisotropia com decaimentos comparáveis com os decaimentos experimentais estão associados a pequenas variações conformacionais de hélice 12. Simulações para dois modelos de apo-PPARγ com a H12 aberta em relação ao corpo do LBD e para as estruturas cristalográficas de apo-RXR e apo-ER, onde a H12 também adota uma conformação aberta, revelaram curvas de anisotropia com decaimentos mais rápidos que os experimentais. Esses resultados implicam em um modelo onde a H12 sofre alterações conformacionais locais, não apresentando variações tão dramáticas como o proposto pelo modelo da ratoeira. / Nuclear Hormone Receptors comprise a protein superfamily responsible for regulation of gene expression. Structurally, they are composed by three domains: a variable N-terminal domain, a highly conserved DNA-binding domain (DBD), and a less conserved C-terminal domain, known as ligand binding domain (LBD). Many experiments have shown that the interaction with ligands affects the structure and the mobility of nuclear receptors C-terminal helix (LBDs Helix 12), being the main mechanism of transcription activation and repression. The first nuclear receptor LBDs structures revealed important differences between ligand bound (holo) and apo-structures concerning the position of the H12: in apo structures, H12 adopted an open conformation, exposing the ligand binding pocket, whereas in holo structures, the H12 was closed, packed over the body of the LBD, burying completely the ligand. This difference suggested a mechanism for ligand entry and exit from the binding pocket called mouse-trap model, however this model has several inconsistencies and has been discredited. Recent experimental and theoretical studies have shown that H12 is more labile in the absence of ligand, but these studies dont provide evidences that the increase in the mobility is associated with the detachment of H12 from the body of the LBD as suggested by the mouse-trap model. Although its clear that H12 is more flexible in the absence of ligands, the size of the conformational changes undergone by H12 is not yet clear. In this work we seek to construct a definitive model for the range of motions that H12 may undergo in the presence or absence of ligand using molecular dynamics simulations. Through direct comparison between molecular dynamics simulations and time-resolved fluorescence anisotropy experiments, we show that experimental observation can only be explained by conformations where the fluorescent probe is interacting with the surface of the PPARγ surface. We also show that simulations with anisotropy decay rates comparable to the experimental decay are associated with small helix 12 conformational changes. Simulations with two models of apo-PPARγ with H12 detached from the body of the LBD and with crystallographic structures of apo-RXR and apo-ER, where the H12 also is in an open conformation, display anisotropy decay rates significantly faster than the experimental ones. These results imply a model for the molecular mobility of the LBD where H12 undergoes local conformational changes and should exhibit dynamic properties less dramatic than proposed by the mouse trap model.

O trabalho apresenta o histórico e o desenvolvimento dos equipamentos de estacas hélice segmentada, que surgiram no ano de 2002. Atualmente já existe um número representativo de equipamentos em operação no mercado, confirmando a boa aceitação do processo pelo meio técnico. São detalhados os aspectos executivos deste tipo de fundação e investiga-se o risco de sua execução no aspecto operacional, no que se refere à integridade da estaca, caso não sejam observados padrões ou regras adequadas pelas empresas executoras. Foram executados ensaios de integridade (PIT) em 10 estacas hélice segmentadas, instaladas em São Bernardo do Campo SP, com particularidades executivas diversificadas e em terreno com características distintas, que permitiram verificar a confiabilidade dos gráficos de monitoração da perfuratriz. Ainda neste trabalho, apresenta-se resultado de prova de carga instrumentada, feita numa estaca hélice segmentada de 30 cm de diâmetro e 12 m de comprimento, instalada no Campo Experimental de Fundações e Mecânica dos Solos da UNICAMP. A estaca foi submetida a carregamentos lento e rápido, estáticos e à compressão, e seus resultados são comparados com os de provas de carga em estacas tipo hélice contínua, de mesmo comprimento, feitas anteriormente no local. Ao término, apresentam-se algumas recomendações baseadas na pesquisa e no acompanhamento de obras, podendo-se assim, avaliar padrões de boa e má execução. / This work presents the history and development of segmented flight auger equipment, which appeared in 2002 in Brasil. Nowadays there is already a considerable number of equipments being operated in the market, confirming the well acceptance of the process in the technical field. The executive aspects on this type of foundation are detailed and it is investigated the risk of its execution in the operational aspect regarding the pile integrity, in case patterns or adequate rules are not observed by the pile companies. Pile integrity tests have been carried out in 10 segmented flight augers installed in São Bernardo do Campo SP, with executive particularities in diversified fields with distinguished characteristics, which allowed to check the reliability of monitoring graphs from the drilling machine. In addition, it is shown the result of an instrumented loading test, carried out on a segmented flight auger of 30 cm diameter and 12 m length, installed at the Experimental Field of Foundation and Soil Mechanics at UNICAMP. The pile was submitted to slow and quick static loading compression tests. A comparison is made with the results of load tests on continuous flight auguer, of the same length, done before on this site. Finally, some recommendations are presented based on the research and on the follow-up of constructions, allowing to evaluate patterns of good and bad execution.

Nous proposons d'explorer dans le cadre de la thèse des solutions originales permettant d'obtenir des caractéristiques de rayonnement peu dépendantes du support de l'antenne. Les antennes étudiées et conçues visent à être utilisées pour des applications GNSS et plus précisément pour des applications multi-bandes du GNSS. Nous les développerons donc en respectant un cahier des charges associé. Deux axes de recherche indépendants sont explorés. Le premier montre les propriétés naturelles d'une antenne composée de plusieurs structures rayonnantes. Nous associons ainsi une structure hélicoïdale équivalente à un dipôle magnétique et un plan métallique équivalent à un dipôle électrique. La taille et les performances de l'antenne ainsi réalisée sont comparables par bien des aspects aux antennes que l'on trouve actuellement dans le commerce pour les applications GNSS. L'antenne réalisée est une antenne mono-bande en polarisation rectiligne ; ce qui n'est pas en accord avec les spécifications de l'application envisagée. Pour compléter cette première étude et satisfaire les exigences d'applications GNSS multi-bandes, nous nous orientons vers une autre technologie qui est exposé dans le second axe. Dans le second axe, nous associons une antenne électrique et un plan réflecteur particulier : une Surface Haute Impédance. L'association de ces deux éléments permet en théorie de réduire l'épaisseur qu'aurait un dispositif classique composé d'une antenne électrique et d'un plan réflecteur métallique. Nous commençons donc par étudier la particularité du plan réflecteur choisi, c'est-à-dire la Surface Haute Impédance. Cette surface étant composé de motifs périodiques nous étudierons le motif qui permet d'obtenir les caractéristiques les plus proches de celles de l'application visée. Nous débutons par une étude en monobande suivi de l'étude d'un motif bi-bande. Le motif mono-bande conçu en simulation présente une très bonne bande-passante (13%) au vue de sa taille minimale (2,5mm). Le motif bi-bande réalisé par imbrication de motifs mono-bande permet d'obtenir en simulation des performances conformes aux attentes dans deux bandes GNSS choisies. L'étude de cette surface se poursuit par une phase de mesure. Le but de l'étude étant de pouvoir placer une antenne au-dessus de la surface fabriquée, une collection d'antennes sera développée afin de régler la surface haute impédance et dans le même temps de tester le dispositif complet. Ainsi dans un premier temps, nous utiliserons des dipôles pour tester et régler la Surface Haute Impédance. Dans cette partie le couplage entre l'antenne et la surface haute impédance placée en-dessous sera notamment étudié. Dans un deuxième temps, afin d'obtenir une polarisation circulaire nous utiliserons d'autres antennes supportant cette polarisation (dipôle croisé et spirale). Dans chaque phase de mesure, le réglage antenne et Surface Haute Impédance sera optimisé et divers paramètres de réglage seront identifiés. Pour les deux axes de recherche, ce sont non seulement le rayonnement que nous cherchons à maîtriser mais aussi la taille de la structure. Ainsi les structures réalisées sont les plus compactes possibles surtout en terme de finesse. Nous concluons sur les performances des antennes réalisées par rapport au cahier des charges et aux autres antennes existantes et exposons les perspectives du travail réalisé / In this thesis, original solutions are proposed for antennas not sensitive to their environment. These antennas are designed for GNSS applications and more precisely for multi-bands ones. So the solutions are developed keeping in mind the GNSS specifications. Two different research axis are discussed. The first one deals with the natural properties of an antenna composed of different radiating structures. So an helix structure is associated with a metallic plate. The specifications of this antenna are in line with the ones of commercial antennas. Nevertheless, this antenna is only one band and in linear polarization which is not conform to the GNSS specifications. To satisfy these specifications a second axis is developed. In this second axis an electric antenna is associated with a specific reflector : a High Impendance Surface. Theorically, this surface allows to place the antenna very close and so reduce the thickness of the whole structure without disturbing the radiation of the antenna. Firstly, the High Impendance Surface and more precisely its periodic patterns is studied. Both one band and dual-band pattern are designed. The one band pattern has a good bandwidth (13%) compared to its size (2,5mm). The dual-band pattern designed by pattern enclosing realized the GNSS specifications in simulation. This is followed by measures. The aim of the thesis is to place the antenna above the designed HIS so a lot of antennas are designed to test and tune the surface. Firstly dipoles are used to study the coupling effects and secondly circular polarized antenna are used to reach the GNSS specifications. For both axis, the radiation pattern and the size of the whole system is optimized. So the proposed solutions are the thinnest ones. To conclude the characteristics of the proposed structures are compared to specifications and to existing antennas and future work is proposed

Resource scarcity obliges humanity to face the problem of identifying efficient ways of distributing them. One way of reducing this problem lies on the possibility of increasing the amount of available goods. Robert Solow's growth theory describes the composition of an economy's output as the sum of units of labor, capital stock and a residual variation called technical change. This residual, the total factors productivity (TFP), is explainable by a series of variables: institutional change, available technology, government policies, etc. This research aimed at finding out the role of institutions in the process of innovation and industrialization in selected emerging countries from 1950 to 2010. Due to its similar historical backgrounds and geographic location, Argentina, Brazil and Mexico were chosen. The last six decades (encompassing the import-substitution industrialization era, the Oil Crisis and the post-Washington Consensus liberalization) were analyzed as a manner of comparing how economic agents reacted to the events of each period. The Triple Helix approach, which takes into consideration the evolutionary relations between governments, firms and universities, was used to map history facts that were compared to the calculated TFP of the given countries. It was demonstrated that the stability of economic and political institutions is a key element for motivating entrepreneurs to innovate. Furthermore, it was noticed a clear difference between the outcomes generated by the different models of economic policy adopted in each period. State intervention was helpful to promote industrial growth but in many occasions its protectionism could not offer enough incentives to motivate entrepreneurial innovation. Many industries faded into State protection and didn't gain enough competitiveness in the global economy. Opening the economy, on the other side, led to the bankruptcy or shrinkage of several firms that were not able to adapt themselves to the international competition but, at the same time, it boosted innovative efforts and, thus, the competitiveness of high technology sectors from emerging economies. Finally, it was noticed that, although many policies were enacted in this direction, the interaction between firms and universities in these countries is still very incipient. / A escassez de recursos obriga a humanidade a enfrentar o problema de identificar formas eficientes para distribuí-los. Uma das formas de reduzir este problema é a possibilidade de aumentar a quantidade de bens disponíveis. A teoria do crescimento de Robert Solow descreve a composição do produto de uma economia como a soma das unidades de trabalho, estoque de capital e uma variação residual chamada mudança técnica. Este resíduo, a produtividade total dos fatores (PTF), é explicável por uma série de variáveis: mudança institucional, tecnologia disponível, políticas governamentais, etc. Esta pesquisa se dedicou a descobrir o papel das instituições no processo de inovação e industrialização em países emergentes selecionados entre 1950 e 2010. Devido às suas similaridades históricas e posicionamento geográfico, Argentina, Brasil e México foram escolhidos. As últimas seis décadas (dividas entre a era da industrialização pela substituição de importações, a Crise do Petróleo e a liberalização pós-Consenso de Washington) foram analisadas de forma a comparar como os agentes econômicos reagiram aos eventos de cada um destes períodos. A abordagem da Hélice Tripla, que leva em consideração as relações evolucionárias entre governos, firmas e universidades, foi usada para mapear fatos históricos que foram comparados com a PTF calculada dos países selecionados. Foi demonstrado que a estabilidade das instituições econômicas e políticas é um elemento chave para motivar empreendedores a inovar. Além disso, percebeu-se uma clara diferenciação entre os resultados gerados pelos modelos de política econômica adotados em cada período. A intervenção estatal foi benéfica para promover o crescimento industrial mas em diversas ocasiões seu protecionismo não ofereceu incentivos suficientes para motivar a inovação empreendedora. Muitas indústrias se perderam em meio a proteção estatal e não obtiveram competitividade suficiente na economia global. A abertura econômica, por outro lado, gerou a falência ou redução de uma série de empresas que não conseguiram se adequar à competição internacional mas, ao mesmo tempo, aumentou os esforços inovadores e, assim, a competitividade de setores de alta tecnologia das economias emergentes. Finalmente, foi notado que, mesmo que diversas políticas tenham sido criadas nesta direção, a interação entre firmas e universidades nestes países permanece muito incipiente.

Made available in DSpace on 2016-04-26T20:24:04Z (GMT). No. of bitstreams: 1 Danilo Fontenele Sampaio Cunha.pdf: 3140013 bytes, checksum: 6f2578bd5ed90f9c088944cd6caadc62 (MD5) Previous issue date: 2015-11-30 / It is argued that understanding the sense of law must be made with an emphasis on discursive inclusiveness and overcome the functionalist paradigms and utilities, aiming to capture the sense of the law through the sense of fair. New view of such phenomenon is suggested, using metaphor created based on the quantum string theory, emphasizing the intimate character of the judge and the weaving of their social bonds. It is stated that the sense of the law is preceded and consists of a sense of fair that precedes and accompanies, presented here in the form of vibrating triple helical helix composed of consciousness, sensitivity and interpretation of the rules and activated by the agent's will constituted by the culture, ethics and interests, according to their freedom and dreams. It is proposed, therefore, to redefine judicial practices in the pursuit of happiness, freedom and equality, overcoming the mere rationalization of the convictions of the judge or of normative guidelines through the use of what we call exlética topical, with the objective of close as possible to the right applicable to the case. It is proposed to finish the resumption of topical sensitivity and poetic in the dynamic conception of the feeling of the fair as a way to reach to human and humane effectuation of the law / Defende-se a ideia de que a compreensão do sentido do Direito deve ser feita com ênfase na inclusividade discursiva e na superação dos paradigmas funcionalistas e utilitários, visando a captar o sentido do Direito mediante a concepção do sentimento do justo. Nova visão de tal fenômeno é sugerida, com utilização de metáfora criada com base na Teoria Quântica das Cordas, enfatizando os caracteres mais íntimos do julgador e a tecedura de seus vínculos sociais. Indica-se que o sentido do Direito é antecedido e composto por um sentimento do justo que o precede e acompanha, aqui denotado na forma de tríplice hélice vibrátil, composta de consciência, sensibilidade e interpretação das normas, bem como ativada pela vontade do agente, constituída pela cultura, ética e interesses, e de acordo com sua liberdade e sonhos. Propõe-se, com efeito, a redefinição de práticas judiciais, na busca da felicidade, liberdade e igualdade, pela superação da mera racionalização das convicções do julgador ou das orientações normativas, mediante a utilização do que se chama de tópica exlética, com o objetivo de aproximar-se o mais possível do justo aplicável ao caso concreto. Sugere-se, ao fim, a retomada da sensibilidade tópica e da poética na concepção dinâmica do sentimento do justo como maneira de se alcançar a efetivação humana e humanitária do Direito

Esta dissertação apresenta uma avaliação do comportamento de estacas hélice contínua quanto à capacidade de carga, ao recalque e à segurança e confiabilidade, a partir de um cenário de análise em que foi considerado um banco de dados de 58 provas de carga estáticas, realizadas em estacas hélice contínua de 13 obras distintas. Esta pesquisa está focada principalmente no comportamento carga-recalque e confiabilidade de fundações em estacas hélice contínua. Nesta análise foi também verificada a aplicabilidade do método proposto por Aoki (1989) para determinação da curva carga-recalque destas provas de carga. Os valores de capacidade de carga medidos foram comparados com os previstos pelos método Aoki & Velloso (1975), o método Decourt & Quaresma (1978), o método de Cabral (1996), e o método Alonso (1996). Estes métodos também foram utilizados para previsão de transferência de carga nas estacas, necessária para a previsão da curva carga-recalque pelos método de Aoki (1989). Adicionalmente, com os resultados das provas de carga foram estimadas para cada obra a probabilidade de ruína da fundação, e de ocorrência de recalques superiores a um valor limite. / This dissertation presents an evaluation of the behavior of continuous flight auger piles on ultimate capacity, settlments, safety and reliability, from a scenario analysis in which we considered a database of 58 static load tests, performed on piles of 13 distinct sites. However, this research is focused on the loaddisplacement behavior and reliability of this type of foundation. This analysis also verified the applicability of the method proposed by Aoki (1989) to determine the load-displacement curve of these pile load tests. The values of measured pile capacity were compared with those provided by the method Aoki & Velloso (1975), the method Decourt & Quaresma (1978), the method Cabral (1996), and the method Alonso (1996). These methods were also used to predict the load transfer along the piles, necessary to predict the load-displacement curve by the method of Aoki (1989). Additionally, the results of these load tests were used to estimate the probability of failure of the foundations tested, and the occurrence of settlements exceeding a threshold value.

Submitted by JOSIANE SANTOS DE OLIVEIRA (josianeso) on 2018-09-24T15:31:37Z No. of bitstreams: 1 Letícia Saltiél Webber_.pdf: 2312766 bytes, checksum: fce9a826a78e0df02fc42136d807f22f (MD5) / Made available in DSpace on 2018-09-24T15:31:37Z (GMT). No. of bitstreams: 1 Letícia Saltiél Webber_.pdf: 2312766 bytes, checksum: fce9a826a78e0df02fc42136d807f22f (MD5) Previous issue date: 2018-05-07 / Nenhuma / O desenvolvimento municipal depende de fatores que afetam a capacidade de gerar emprego e renda, de aumentar suas receitas e de realizar investimentos. Esse problema envolve várias forças sociais como o governo, as entidades que promovem o conhecimento, os empresários e a sociedade. Com a intenção de modificar o ambiente no qual se vive e auxiliar o município de Osório/RS a encontrar alternativas para amenizar os problemas locais, idealizou-se a implementação de um parque tecnológico na cidade. O município carece de um norteamento para a implantação do parque tecnológico, dessa forma, para a efetivação dessa iniciativa, apresenta-se o objetivo dessa dissertação, que é propor um roteiro indicando quais as diretrizes necessárias para a criação de um parque tecnológico para o município de Osório e a forma de sensibilização dos atores da tríplice hélice e da sociedade. A proposta contempla um roteiro de procedimentos que devem ser executadas para viabilizar a implementação do parque, inspirado no modelo de governança da tríplice hélice. O cumprimento dos objetivos foi possível através da pesquisa documental com abordagem exploratória qualitativa, que permitiu o acesso e análises de dados; da pesquisa-ação, que promoveu a interação dos atores envolvidos; e teve o direcionamento dos passos para a criação do roteiro conforme a Design Science Research com as sugestões dos Experts. Essa movimentação pôde ser registrada num Caderno de Campo. Com a pesquisa, foi possível observar que o município apresenta um desenvolvimento regular motivado principalmente pela falta de investimentos e que necessita aumentar o emprego e a renda, que diminuíram em função da diminuição da capacidade produtiva e do envelhecimento da população. Ainda que, a implantação do parque tecnológico estruturante voltado para tecnologia, com governança nos moldes da tríplice hélice, auxiliaria no desenvolvimento local, consoante as sugestões dos Experts. Assim, o roteiro proposto para a criação do parque tecnológico já logrou êxito visto que várias etapas propostas já foram realizadas. / The municipal development depends on factors that affect the ability to generate jobs and income, to increase their revenue and undertake investments. This problem involves various social forces as the Government, entities that promote knowledge, entrepreneurs and the society. With the intent to modify the environment in which one lives and assist the municipality of Osório/RS to find alternatives to alleviate local problems, idealized implementation of a technological park in the city. The city lacks a providing guidance for the implementation of the technology park, in this way, for the implementation of this initiative, the goal of this dissertation is to propose a roadmap indicating what the guidelines required for the creation of a park technology for the city of Osório and the form of awareness of the triple helix and actors of society. The proposal includes a script for procedures that must be performed to enable implementation of the Park, inspired by the model of governance of the triple helix. The achievement of the goals was possible through documentary research with exploratory qualitative approach, which allowed the access and analysis of data; the action research, which promoted the interaction of actors involved; and had the direction of the steps to the creation of the script as a Design Science Research with suggestions from Experts. This movement could be recorded in a field Notebook. With the survey, it was possible to observe that the municipality presents a regular development motivated principally by lack of investment and that it needs to increase employment and income, which decreased due to the decrease in production capacity and the aging of the population. Although the deployment of structuring technology-oriented technology park, with governance along the lines of the triple helix, would assist in local development, according to the suggestions of Experts. Thus, the proposed roadmap for the creation of the technological park has already achieved success since several steps have already been made proposals.

Les foldamères sont des architectures moléculaires synthétiques repliées, inspirées par les structures et les fonctions des biopolymères naturels. Le repliement est un processus sélectionné par la nature pour contrôler la conformation de sa machinerie moléculaire afin de réaliser des tâches chimiques ou mécaniques. Durant les dix dernières années de recherche sur les foldamères, des oligomères synthétiques, capables d'adopter des conformations repliées bien définies et prévisibles, comme des hélices, ont été proposés. Les progrès récents ont montré que la synthèse chimique par étapes et le design moléculaire basé sur un squelette oligoamide aromatique permettaient de produire des architectures moléculaires repliées de manière hélicoïdale. La forme du squelette et sa rigidité, des préférences conformationnelles locales, des interactions spécifiques entre monomères éloignés dans une séquence, ainsi que l'action de paramètres externes comme le solvant, ou la présence d'ions peuvent être combinés pour induire une tendance au repliement. Ces architectures sont remarquables car elles peuvent donner lieu à des motifs de repliement qui n'ont pas d'équivalent dans les structures des biopolymères naturels. Par exemple, des hélices dont le diamètre varie le long de la séquence, ou des hélices possédant un centre d'inversion du pas, des hélices en chevrons,... ont été rapportées. Alors que les structures de ces molécules hélicoïdales ont été abondamment caractérisées à l'état solide par cristallographie des rayons X, leur comportement en solution, et surtout le comportement dynamique, est très peu connu. Leurs propriétés mécano-chimiques sont quant à elles inconnues à ce jour. L'objectif du projet est de synthétiser différentes molécules synthétiques hélicoïdales de type oligoamide aromatique et d'obtenir une description détaillée de leur conformation dynamique en solution, ainsi que de leurs propriétés mécano-chimiques, par spectroscopie de force sur molécule unique basée sur l'AFM. / Foldamers are artificial folded molecular architectures inspired by the structures and functions of natural biopolymers. Folding is the process selected by nature to control the conformation of its molecular machinery to carry out chemical functions and mechanical tasks, such as en-zyme catalysis, duplication in nucleic acids, force generation,... During the last decade of research on foldamers, synthetic oligomers able to adopt well- defined and predictable folded conformations, such as helices, have been proposed. Recent progress has shown that stepwise chemical synthesis and molecular design based on aromatic oligoamide backbones enable to produce large helically folded molecular architectures. The shape and stiffness of the backbone, local conformational preferences, specific interactions between distant monomers in sequences, as well as the action of external parameters such as the solvent or the presence of ions, can be combine to induce folding tendency. A remarkable aspect of these architectures is that they can give rise to folded patterns that have no in natural counterparts biopolymer structures. For instance, helices whose diameter varies along the se-quence, helices possessing a handedness inversion centre, herringbone helices have been reported. While the structures of these helical molecules have been well characterized in the solid state by X-ray crystallography, much less is known about their dynamic behavior in solution. Their mechanochemical properties are unknown. The objective of the project is to synthesize various helical nanorchitectures based on an oli-goamide aromatic backbone and to obtain a detailed picture of their dynamical conformation in solution, as well as, their mechanochemical properties, by AFM-based single molecule force spectroscopy.

Au cours de ces dernières années, les communications sans fil connaissent une croissance vertigineuse, avec le développement de standards de communication de plus en plus nombreux, qui ouvrent la voie à de multiples applications telles que : la téléphonie mobile, le biomédical, le maritime, le civil et le militaire. De nos jours, les communications sans fil se sont diversifiées et multipliées. Cela entraîne la conception d’antennes toujours plus innovantes, performantes et de taille de plus en plus réduite (miniaturisation). Le projet FLEXBEA (FLEXible BEAcon) a pour but le développement d’un nouveau concept de balises de détresse miniatures (AIS et COSPAS-SARSAT), faible coût, intégrées dans des équipements de sécurité maritime tels qu’un radeau de survie et un gilet de sauvetage. Ces équipements sont destinés aux professionnels de la mer et aux plaisanciers. L’atout majeur de ce nouveau concept est l’intégration dans des équipements de sécurité maritime d’une fonction de détresse en cas de problème majeur : homme à la mer (MOB, Man OverBoard) par exemple lors d’un naufrage. Différentes antennes ont été étudiées. Nous présentons des antennes planaires (de type dipôle ou monopôle imprimé) développées dans la bande UHF : une solution de dipôle avec brins repliés est proposée afin de réduire l'encombrement, et deux modes d'alimentation (symétrique / dissymétrique) sont comparés. Des exemples d'antenne monopôle sont ensuite présentés avec une modification de leur géométrie (structures de type Bow-tie ou méandre) pour assurer une miniaturisation optimale. Puis les antennes filaires retenues pour le projet, avec une modélisation de ces antennes par un circuit équivalent (RLC). Des formules analytiques sont proposées afin de déterminer les valeurs de composants RLC qui interviennent dans le modèle circuit. Ensuite, nous sommes passés à la conception de l’antenne de la balise. Deux antennes ont été conçues et mesurées. Un monopôle ruban avec introduction de composants localisés pour la balise AIS et COSPAS-SARSAT, et une antenne hélice fonctionnant dans la bande AIS, intégrée dans la balise "SIMY". De nombreuses réalisations et mesures ont été effectuées pour caractériser ses antennes. / Over the last few years, wireless communications have grown dramatically, with the development of more and more communication standards, which open the way to multiple applications such as: mobile telephony, biomedical, maritime, the civilian and the military. Today, wireless communications have diversified and multiplied. This leads to the design of antennas that are always more innovative, more efficient and smaller in size (miniaturization). The FLEXBEA project (FLEXible BEAcon) aims to develop a new concept of low cost miniature distress beacons (AIS and COSPAS-SARSAT) integrated into marine safety equipment such as a life raft and a lifejacket safety. This equipment is intended for professionals of the sea and boaters. The main advantage of this new concept is the integration in maritime safety equipment of a distress function in case of major problem: man overboard (MOB, Man OverBoard) for example during a shipwreck. Different antennas have been studied. We present planar antennas (dipole type or printed monopoly) developed in the UHF band: a dipole solution with folded strands is proposed to reduce the bulk, and two modes of supply (symmetrical / asymmetrical) are compared. Examples of monopole antennas are then presented with a modification of their geometry (Bow-tie or meander type structures) to ensure optimal miniaturization. Then the wired antennas selected for the project, with a modeling of these antennas by an equivalent circuit (RLC). Analytical formulas are proposed to determine the RLC component values ​​involved in the circuit model. Then we went to the design of the beacon antenna. Two antennas were designed and measured. A ribbon monopoly with introduction of localized components for the AIS and COSPAS-SARSAT beacon, and a helix antenna operating in the AIS band, integrated into the "SIMY" beacon. Many achievements and measurements have been made to characterize its antennas.

Les organismes vivants produisent des peptides antimicrobiens (PAMs) pour se protéger contre les microbes. La résistance croissante aux antibiotiques nécessite le développement de nouvelles stratégies thérapeutiques et les PAMs sont des candidats prometteurs pour résoudre ce problème. Ils possèdent une activité à large spectre et leur principal mécanisme d'action par perméation de la membrane engendre peu de phénomènes de résistance. Néanmoins, leur faible biodisponibilité empêche leur utilisation. Certaines limitations peuvent être surmontées en développant des mîmes de PAMs qui conservent leur activité mais avec un potentiel thérapeutique accru. Les peptoïdes (oligomères de N-alkylglycine) structurés en hélice cationique amphiphile sont de bons mimes de PAMs. Les peptoïdes sont plus flexibles que les peptides en raison de l'isomérie cis/trans des amides N,N-disubstitués ; cependant la conformation des amides peut être contrôlée par un choix judicieux des chaînes latérales. Le but de cette thèse est d'étudier l'influence de chaînes latérales(hydrophobes ou cationiques) bloquant la conformation des amides en cis et induisant une structure hélicoïdale de type PolyProline I (PPI) robuste, sur l’activité antibactérienne et la sélectivité de peptoïdes. La conception, la synthèse et l’étude conformationnelle de nouveaux oligomères peptoïdes cationiques portant des chaînes latérales de type tert-butyle et/ou triazolium ont été réalisées. Dans un premier temps, la synthèse en solution d'oligomères à base de tert-butyle a été développée puis une stratégie de synthèse en phase solide a été mise en place pour accéder aux oligomères à base de 1,2,3-triazolium. Ensuite, ces nouveaux oligomères ont été évalués pour leur activité vis à vis d’un panel de bactéries Gram-positive et Gram-négative, leur l'activité antibiofilm et leur sélectivité cellulaire. Enfin, pour visualiser les effets des peptoïdes amphiphiles sur les bactéries, une étude de microscopie a été réalisée. / Living organisms produce antimicrobial peptides (AMPs) to protect themselves against microbes.The growing problem of antimicrobial resistance calls for new therapeutic strategies and the natural AMPs have shown ground-breaking potential to address that issue. They show broad-spectrum activity and their main mechanism of action by bacterial cell membrane disruption implies low emergence of resistance which makes them potent candidates for replacing conventional antibiotics. Nevertheless, few hurdles are impeding their use, notably poor bioavailability profile. Some of these limitations can be overcome by developing peptidomimetics of AMPs which exhibit antibacterial activities together with enhanced therapeutic potential. Peptoids (i.e. N-alkyl glycine oligomers) adopting cationic amphipathic helical structures are mostly competent AMP mimetics. From a conformational point of view, peptoids are fundamentally more flexible than peptides primarily due to the cis/trans isomerism of N,N-disubstituted amides but studies in this area have shown that cis amide conformation can be controlled by careful choice of side-chain to set a PolyProline I-type helical structure of peptoids. In this thesis, the genesis of novel amphipathic cationic peptoids carrying cis-directing tert-butyl and/or triazolium-type side-chains and their untapped potential to act against bacteria will be discussed comprehensively. First, the solutionphase synthesis of tert-butyl-based oligomers was developed. Second, novel method of solid-phase submonomer synthesis was optimised to access 1,2,3-triazolium-based oligomers. Then, the synthesised cationic oligomers were evaluated for their antibacterial potential, followed by antibiofilm activity and cell selectivity assays. In the end, to have insights on the mode of action of amphipathic peptoids, microscopy was carried out.